The 14‐day repeated‐dose toxicity study of a fixed‐dose combination, QXOH/levobupivacaine, via subcutaneous injection in beagle dogs

2020 ◽  
Author(s):  
Jie Zhang ◽  
YuJun Zhang ◽  
Qinqin Yin ◽  
Jun Yang ◽  
Yi Kang ◽  
...  
Keyword(s):  
Subcutaneous Injection ◽  
Toxicity Study ◽  
Fixed Dose Combination ◽  
Repeated Dose ◽  
Fixed Dose ◽  
Beagle Dogs ◽  
Repeated Dose Toxicity ◽  
Dose Combination

Intravenous repeated-dose toxicity study of ZnPcS2P2-based-photodynamic therapy in beagle dogs

2007 ◽  
Vol 47 (3) ◽  
pp. 221-231 ◽  
Author(s):  
Wei Liu ◽  
Naisheng Chen ◽  
Hongtao Jin ◽  
Jinling Huang ◽  
Jinfeng Wei ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Toxicity Study ◽  
Repeated Dose ◽  
Beagle Dogs ◽  
Repeated Dose Toxicity

Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive breast cancer: A multidisciplinary approach

2021 ◽  
pp. 107815522199971
Author(s):  
Barbara DuMond ◽  
Vidhi Patel ◽  
Anne Gross ◽  
Anita Fung ◽  
Susan Weber
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Subcutaneous Injection ◽  
Fixed Dose Combination ◽  
Phase Iii ◽  
Fixed Dose ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Dose Combination ◽  
Positive Breast Cancer

Pertuzumab plus trastuzumab, administered intravenously (IV) with chemotherapy, is standard treatment for HER2-positive metastatic or high-risk early breast cancer. Pertuzumab and trastuzumab are administered over 1–2.5 h traditionally; however, the need for IV infusions places a strain on medical centers with respect to scheduling, preparation, and administration. A novel fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PHESGO®, PH FDC SC) can be administered in approximately 5–8 min. PH FDC SC was non-inferior to IV pertuzumab plus trastuzumab in terms of pertuzumab and trastuzumab serum levels in the phase III FeDeriCa study, which enrolled 500 patients with HER2-positive early breast cancer. Total pathologic complete response rates were comparable after PH FDC SC (59.7%) or IV pertuzumab plus trastuzumab (59.5%), as was the incidence of grade ≥3 (48.8% vs 52.8%) and serious adverse events (16.1% vs 17.9%). The results of a phase II clinical trial (PHranceSCa) showed that a majority of patients (85%) preferred PH FDC SC treatment over IV pertuzumab plus trastuzumab. A US multicenter expanded access study (NCT04395508) is evaluating the safety of PH FDC SC administered at home by nurse providers in patients receiving maintenance HER2-targeted therapy every 3 weeks. This product takes much less time to administer than IV pertuzumab–trastuzumab and has the potential to alleviate time constraints for patients and busy clinics. In this review we provide an overview of PH FDC SC, and discuss our experience in preparing and administering this product to patients with HER2-positive breast cancer during clinical trials.

scholarly journals Population pharmacokinetic and exploratory exposure–response analysis of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer in the FeDeriCa study

2021 ◽  
Author(s):  
Bei Wang ◽  
Rong Deng ◽  
Stefanie Hennig ◽  
Tanja Badovinac Crnjevic ◽  
Monika Kaewphluk ◽  
...  
Keyword(s):  
Subcutaneous Injection ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Comparable Efficacy ◽  
Lean Body Weight ◽  
Response Analysis ◽  
Population Pharmacokinetic ◽  
Efficacy And Safety ◽  
Exposure Response ◽  
Dose Combination

Abstract Purpose To characterize pertuzumab pharmacokinetics (PK) in FeDeriCa (NCT03493854: fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection [PH FDC SC] versus intravenous pertuzumab plus trastuzumab); derive individual pertuzumab exposures in the PH FDC SC arm for subsequent pertuzumab exposure–response (ER) analyses; compare observed trastuzumab PK with predicted exposures from a previous SC trastuzumab model; assess whether pertuzumab affects trastuzumab PK; evaluate pertuzumab exposure–efficacy and –safety relationships and support the approved SC dosing regimen. Methods Population pharmacokinetic modeling and simulations were used to describe the data. Standard goodness-of-fit diagnostics and prediction-corrected visual predictive checks were used for model performance assessment. Covariates were included from previously reported models. ER analysis was conducted using logistic regression. Results SC pertuzumab PK was described adequately by a two-compartment model with first-order absorption; significant covariates included in the final model were albumin, lean body weight, and Asian region; however, these appeared not to be clinically relevant. Trastuzumab concentrations were described adequately by the previous model; there was no evidence of a pertuzumab effect on trastuzumab PK as part of PH FDC SC and higher model-predicted pertuzumab exposure was not associated with differences in pathologic complete response rate or an increased probability of selected grade ≥ 3 adverse events of interest. Conclusion The approved PH FDC SC dose [loading: 1200/600 mg pertuzumab/trastuzumab (15 mL); maintenance: 600 mg pertuzumab/trastuzumab (10 mL) and 2000 U/mL recombinant human hyaluronidase every 3 weeks] provides a positive benefit–risk profile with comparable efficacy and safety to intravenous pertuzumab plus trastuzumab.

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